Integration of proteomic aging clocks in a phase 2a clinical trial supports simultaneous geroprotective assessment

Alex Zhavoronkov and colleagues analyzed serum proteomes from 42 participants in a 12-week phase 2a trial of rentosertib for idiopathic pulmonary fibrosis. Six independently developed proteomic clocks, including ProtAge, OrganAge, PAC, ipfP3GPT, and PAOPAC, consistently predicted lower biological-age values in treated arms than in placebo. Pathway analyses suggested shifts in senescence and metabolic processes alongside the drug’s anti-fibrotic activity. The result is useful as a trial-design demonstration: aging biomarkers can be embedded in disease trials without waiting for mortality endpoints. It is not evidence that rentosertib reverses aging. The participants had a serious age-related lung disease. Proteomic clocks can respond to disease activity, inflammation, organ injury, or treatment effects. The authors state that the clocks alone cannot separate an aging effect from an IPF-specific effect. The analysis used a small secondary sample and lasted 12 weeks. Rentosertib is investigational and is not an anti-aging treatment. The study supports measuring biological-age markers in controlled trials, with clinical outcomes and disease-specific controls required before geroprotective claims.

This work supports the goal of dual-purpose clinical trial designs that integrate aging endpoints into studies for specific disease indications.